Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression

Maria C. Demaria; Louisa Yeung; Rens Peeters; Janet L. Wee; Masa Mihaljcic; Eleanor L. Jones; Zeyad Nasa; Frank Alderuccio; Pamela Hall; Brodie C. Smith; Katrina J. Binger; Gunther Hammerling; Hang Fai Kwok; Andrew Newman; Ann Ager; Annemiek van Spriel; Michael J. Hickey; Mark D. Wright

doi:10.1016/j.isci.2020.101104

Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression

Maria C. Demaria, Louisa Yeung, Rens Peeters, Janet L. Wee, Masa Mihaljcic, Eleanor L. Jones, Zeyad Nasa, Frank Alderuccio, Pamela Hall, Brodie C. Smith, Katrina J. Binger, Gunther Hammerling, Hang Fai Kwok, Andrew Newman, Ann Ager, Annemiek van Spriel, Michael J. Hickey, Mark D. Wright

Research output: Contribution to journal › Article › Research › peer-review

27 Citations (Scopus)

Abstract

Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53^−/− mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53^−/− B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53^−/− B cells and reduced stability of L-selectin on Cd53^−/− T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53^−/− mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

Original language	English
Article number	101104
Number of pages	21
Journal	iScience
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.isci.2020.101104
Publication status	Published - 22 May 2020

Keywords

Immune Response
Immunology
Molecular Mechanism of Behavior
Specialized Functions of Cells

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310089716-oaFinal published version, 3.53 MBLicence: CC BY-NC-ND

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Demaria, M. C., Yeung, L., Peeters, R., Wee, J. L., Mihaljcic, M., Jones, E. L., Nasa, Z., Alderuccio, F., Hall, P., Smith, B. C., Binger, K. J., Hammerling, G., Kwok, H. F., Newman, A., Ager, A., van Spriel, A., Hickey, M. J., & Wright, M. D. (2020). Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression. iScience, 23(5), Article 101104. https://doi.org/10.1016/j.isci.2020.101104

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title = "Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression",

abstract = "Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53−/− mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53−/− B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53−/− B cells and reduced stability of L-selectin on Cd53−/− T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53−/− mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.",

keywords = "Immune Response, Immunology, Molecular Mechanism of Behavior, Specialized Functions of Cells",

author = "Demaria, {Maria C.} and Louisa Yeung and Rens Peeters and Wee, {Janet L.} and Masa Mihaljcic and Jones, {Eleanor L.} and Zeyad Nasa and Frank Alderuccio and Pamela Hall and Smith, {Brodie C.} and Binger, {Katrina J.} and Gunther Hammerling and Kwok, {Hang Fai} and Andrew Newman and Ann Ager and {van Spriel}, Annemiek and Hickey, {Michael J.} and Wright, {Mark D.}",

year = "2020",

month = may,

day = "22",

doi = "10.1016/j.isci.2020.101104",

language = "English",

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Demaria, MC, Yeung, L, Peeters, R, Wee, JL, Mihaljcic, M, Jones, EL, Nasa, Z, Alderuccio, F, Hall, P, Smith, BC, Binger, KJ, Hammerling, G, Kwok, HF, Newman, A, Ager, A, van Spriel, A, Hickey, MJ & Wright, MD 2020, 'Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression', iScience, vol. 23, no. 5, 101104. https://doi.org/10.1016/j.isci.2020.101104

TY - JOUR

T1 - Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression

AU - Demaria, Maria C.

AU - Yeung, Louisa

AU - Peeters, Rens

AU - Wee, Janet L.

AU - Mihaljcic, Masa

AU - Jones, Eleanor L.

AU - Nasa, Zeyad

AU - Alderuccio, Frank

AU - Hall, Pamela

AU - Smith, Brodie C.

AU - Binger, Katrina J.

AU - Hammerling, Gunther

AU - Kwok, Hang Fai

AU - Newman, Andrew

AU - Ager, Ann

AU - van Spriel, Annemiek

AU - Hickey, Michael J.

AU - Wright, Mark D.

PY - 2020/5/22

Y1 - 2020/5/22

N2 - Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53−/− mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53−/− B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53−/− B cells and reduced stability of L-selectin on Cd53−/− T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53−/− mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

AB - Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53−/− mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53−/− B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53−/− B cells and reduced stability of L-selectin on Cd53−/− T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53−/− mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.

KW - Immune Response

KW - Immunology

KW - Molecular Mechanism of Behavior

KW - Specialized Functions of Cells

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DO - 10.1016/j.isci.2020.101104

M3 - Article

AN - SCOPUS:85084467729

SN - 2589-0042

VL - 23

JO - iScience

JF - iScience

IS - 5

M1 - 101104

ER -

Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression

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Keywords

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NHMRC Research Fellowship

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Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression

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Keywords

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NHMRC Research Fellowship

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